The increased alveolar epithelial and pulmonary microvascular permeability found in the adult respiratory distress syndrome has been attributed to humoral, cellular, and/or neural agents either alone or in combination. Loss of alveolar capillary membrane (ACM) fixed negative charges has not previously been considered. Our ongoing investigations confirm that ACM negative charges are an important factor in normal molecular permselectivity. Loss of these fixed negative charges leads to increased flux of anionic dextrans. This project will extend these observations and confirm that the liquid filled alveolus has a negative transalveolar electrical potential difference which is lost following ethchlorvynol injection or endotoxin infusion. We will attempt to correct the loss of negativity by placing 5% unlabelled 500,000 MW dextran SO4 (highly anionic) solution in the lung to decrease the flux of anionic proteins from blood to liquid filled lung. Employing the right lymph duct model, we will nebulize this dextran SO4 diffusely throughout the lung fields and measure the transalveolar flux of anionic dextran during control, ethchlorvynol injection and endotoxin infusion. If the intrapulmonic nebulization of dextran SO4 impedes the flux of anionic molecules this may be a rational therapeutic modality to employ in patients with ARDS.